The ageing world population faces a coming pandemic of high-risk coronary artery disease (CAD). Patients with CAD have 3 therapeutic options, which are based on objective clinical outcome: medical therapy and risk factor modification (Medicine), and 2 forms of revascularization, coronary artery bypass graft surgery (CABG), and percutaneous coronary intervention (PCI). More than 50 large (>100 patients), multicenter, prospective, randomized clinical trials (RCT) have compared these treatment options in terms of clinical benefits and patient risks. The randomized trials which demonstrated hard outcome (survival, myocardial infarction, stroke) benefits from statins, angiotensin-converting enzyme inhibition and thienopyridines have all been completed subsequent to the publication of most Medicine versus revascularization trials. These medical therapies, plus aspirin, beta-blockers, and risk factor modification, should be made available to patients regardless of the decision to revascularize, or the decision by what means (CABG or PCI). This review integrates the information from these trials, comparing the clinical benefits against the risks inherent in the 3 therapeutic options. The results of our review show that: trials of medicine versus revascularization (either CABG or PCI) support the revascularization paradox, in that the patients at highest risk of adverse outcome, from myocardial ischemia, have a hard outcome benefit (survival, MI, or stroke) from revascularization. This paradox, first seen in the Medicine versus CABG trials of the 1970s, is evident in the trials comparing fibrinolysis and other medicines, with primary PCI for ST-elevation myocardial infarction (MI). The paradox is evident in the conservative versus invasive strategy trials of non-ST-elevation MI and unstable angina, where the benefit of revascularization occurs only in high-risk subsets. The paradox often results in sicker patients, who have more to gain from revascularization, being denied it because of the elevated perception of risk (comparable to a reperfusion paradox in ST-elevation MI, where patients most likely to benefit from thrombolytics are denied them because of the perception of risk). Trials that compared medicine with revascularization for the treatment of acute MI support the use of PCI as the preferred early stabilization strategy (90% of all PAMI trial patients). The majority of the PCI versus CABG trials enrolled populations that were at relatively low risk for ischemic clinical events. These trials demonstrated few hard outcome (survival, MI, or stroke) differences between CABG and PCI. On the basis of the results obtained the following conclusions may be drawn: medicines are the primary options for stable, low-risk CAD, and should be given to all CAD patients. Medically refractory is a useful high-risk marker of potential benefit from revascularization. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD, in part because of its application to chronic occlusions. PCI is the acute stabilization method of choice for patients with on-going ischemia and acute MI, especially among patients with hemodynamic compromise, and/or major comorbidity.